ORCID Profile
0000-0002-4620-9577
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Publisher: Cold Spring Harbor Laboratory
Date: 19-08-2021
DOI: 10.1101/2021.08.18.456677
Abstract: Previous studies indicate a role of dopamine in hippoc us-dependent spatial navigation. Although neural representations of direction are an important aspect of spatial cognition, it is not well understood whether dopamine directly affects these representations, or only impacts other aspects of spatial brain function. Moreover, both dopamine and spatial cognition decline sharply during age, raising the question which effect dopamine has on directional signals in the brain of older adults. To investigate these questions, we used a double-blind cross-over L-DOPA/Placebo intervention design in which 43 younger and 37 older adults navigated in a virtual spatial environment while undergoing functional magnetic resonance imaging (fMRI). We studied the effect of L-DOPA, a DA precursor, on fMRI activation patterns that encode spatial walking directions that have previously been shown to lose specificity with age. This was done in predefined regions of interest, including the early visual cortex, retrosplenial cortex, and hippoc us. Classification of brain activation patterns associated with different walking directions was improved in the hippoc us and the retrosplenial cortex following L-DOPA administration. This suggests that DA enhances the specificity of neural representations of walking direction in these areas. In the hippoc us these results were found in both age groups, while in the RSC they were only observed in younger adults. Taken together, our study provides evidence for a mechanistic link between DA and the specificity of neural responses during spatial navigation. The sense of direction is an important aspect of spatial navigation, and neural representations of direction can be found throughout a large network of space-related brain regions. But what influences how well these representations track someone’s true direction? Using a double-blind cross-over L-DOPA/Placebo intervention design, we find causal evidence that the neurotransmitter dopamine impacts the fidelity of direction selective neural representations in the human hippoc us and retrosplenial cortex. Interestingly, the effect of L-DOPA was either equally present or even smaller in older adults, despite the well-known age related decline of dopamine. These results provide novel insights into how dopamine shapes the neural representations that underlie spatial navigation.
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.NEUROIMAGE.2022.119670
Abstract: Previous studies indicate a role of dopamine in spatial navigation. Although neural representations of direction are an important aspect of spatial cognition, it is not well understood whether dopamine directly affects these representations, or only impacts other aspects of spatial brain function. Moreover, both dopamine and spatial cognition decline sharply during age, raising the question which effect dopamine has on directional signals in the brain of older adults. To investigate these questions, we used a double-blind cross-over L-DOPA/Placebo intervention design in which 43 younger and 37 older adults navigated in a virtual spatial environment while undergoing functional magnetic resonance imaging (fMRI). We studied the effect of L-DOPA, a dopamine precursor, on fMRI activation patterns that encode spatial walking directions that have previously been shown to lose specificity with age. This was done in predefined regions of interest, including the early visual cortex, retrosplenial cortex, and hippoc us. Classification of brain activation patterns associated with different walking directions was improved across all regions following L-DOPA administration, suggesting that dopamine broadly enhances neural representations of direction. No evidence for differences between regions was found. In the hippoc us these results were found in both age groups, while in the retrosplenial cortex they were only observed in younger adults. Taken together, our study provides evidence for a link between dopamine and the specificity of neural responses during spatial navigation. SIGNIFICANCE STATEMENT: The sense of direction is an important aspect of spatial navigation, and neural representations of direction can be found throughout a large network of space-related brain regions. But what influences how well these representations track someone's true direction? Using a double-blind cross-over L-DOPA/Placebo intervention design, we find causal evidence that the neurotransmitter dopamine impacts the fidelity of direction selective neural representations in the human hippoc us and retrosplenial cortex. Interestingly, the effect of L-DOPA was either equally present or even smaller in older adults, despite the well-known age related decline of dopamine. These results provide novel insights into how dopamine shapes the neural representations that underlie spatial navigation.
No related grants have been discovered for Christoph Koch.